Effectiveness versus efficacy of conjugated pneumococcal vaccine: a systematic review of randomised, controlled trials with meta-analysis examining absolute risk reduction and relative risk
Word Text: Clinical Microbiology and Infection (CMI) and the International Journal of Antimicrobial Agents (IJAA), the official journals of ESCMID and ISC . (Abstract accepted for presentation 9/5/2011 and publication
Numbers Needed to Treat (NNT) is a measure of the effectiveness. In the context of newer vaccines it is good to ask how many children need to be vaccinated so that one life is saved - the NNT of the vaccine. This is sometimes called the Numbers Needed to Vaccinate (NNV)
The next question is related to the cost: How much does it cost to vaccinate one child with this new vaccine.
Once we have these 2 figures we can easily calculate the cost per life saved.
We did a meta analysis (a study of all the studies available) to look at Pneumococcal vaccine. The vaccine has very poor efficacy that the NNT to save one life could not be calculated. Instead we calculated the NNT to prevent one case of clinical pneumonia - (a condition that is usually easily treated with very inexpensive medicines). This allows the cost of prevention with vaccine to be compared to the cost of treatment with simple antibiotics.
There was a small but statistically significant benefit of vaccination on clinical pneumonia (OR=0.927, 95%CI 0.885-0.971, NNT=200), radiological pneumonia (OR=0.749; 95%CI 0.682-0.822, NNT=143) and invasive disease caused by vaccine serotypes (OR=0.215, 95%CI 0.149-0.311, NNV=500).
The small benefit in terms of reduction of clinical pneumonia is also offset by an increase in Asthma (0.001, 95% CI 0.000 to 0.002, p=0.007, NNT=1000).
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Effectiveness versus efficacy of conjugated pneumococcal vaccine: a systematic review of randomized controlled trials with meta-analysis examining absolute risk reduction and relative risk.
Objectives
Use of the 7-valent pneumococcal conjugate vaccine (PCV7) resulted in reduction in vaccine serotypes invasive pneumococcal disease (IPD). However, IPD due to serotypes not included in the PCV7 increased in frequency. This prompted the introduction of a 13 valent vaccine. Previous systematic reviews have examined vaccine efficacy (odds ratio and relative risk). However, effectiveness of PCV in reducing childhood morbidity and mortality (in terms of absolute risk reduction (ARR) and numbers needed to treat (NNT)) has not been published. At the threshold of introducing the PCV13, such an assessment of the old vaccine is useful for comparison. The objective here was to evaluate the effectiveness of PCV through a systematic review of literature.
Methods
Systematic literature search for randomized controlled trials reporting on measures of vaccine effectiveness (invasive Pneumococcal disease, pneumonia, meningitis, all-cause mortality, Pneumococcal disease specific mortality, and systemic adverse events/effects) was undertaken and data extracted based on a priori criteria. Data were analysed to calculate odds ratio, relative risk and absolute risk reduction (ARR); and pooled through meta-analysis. Number needed to treat (vaccinate) was calculated for effectiveness.
Results
There were five methodologically good trials presenting data through 11 publications. There was a small but statistically significant benefit of vaccination on clinical pneumonia (OR=0.927, 95%CI 0.885-0.971, NNT=200), radiological pneumonia (OR=0.749; 95%CI 0.682-0.822, NNT=143) and invasive disease caused by vaccine serotypes (OR=0.215, 95%CI 0.149-0.311, NNV=500). The effect on all-cause mortality was OR and RR=0.88, 95%CI 0.78 to 0.99, and RD 0.00, 95%CI -0.01 to 0.00 (NNT cannot be calculated). There was no difference in invasive Pneumococcal disease caused by vaccine-related and vaccine-unrelated serotypes. There was no data on meningitis and Pneumococcal disease-specific mortality. Examination of multiple adverse events did not show a difference in risk compared to control, except for a small but statistically significant increase in risk of asthma.
Conclusion
PCV7 appears to have limited effectiveness against pneumonia; but does not reduce all-cause mortality. There is significant reduction in vaccine serotype IPD. There is no data to draw conclusions for other clinical problems of public health significance such as meningitis, and Pneumococcal disease-specific mortality.